Catalyst for a Cure: 2018 Research Progress

The Catalyst for a Cure Biomarker Initiative funded by Glaucoma Research Foundation is a collaborative research project that is accelerating the pace of discovery toward better treatments and ultimately a cure for glaucoma. Catalyst for a Cure (CFC) brings together four laboratories with complementary skill sets spanning neuroscience, optical imaging, biomedical engineering, and clinical ophthalmology.

The principal investigators are Alfredo Dubra, PhD, Jeffrey L. Goldberg, MD, PhD, Andrew Huberman, PhD, and Vivek Srinivasan, PhD. Learn about their recent progress in this video that was first presented at the Glaucoma 360 Annual Gala on February 8, 2018 in San Francisco.

Video Transcript

Dr. Srinivasan: Over the past five years we've put a lot of work, the whole team, into learning the basic science of glaucoma, into really finding out what are the earliest changes in the disease. We built instrumentation to detect those changes early, and tested them in human subjects.

I think the most important, impactful moment for me was when we actually took one of the instruments we built and put it in the ophthalmology clinic. When the first patient came in and sat down, it really hit me how all of that work was really coming to fruition and that we were finally going to use some of this knowledge to help benefit patients.

Dr. Dubra: By definition, glaucoma is a disease that affects the ganglion cells. Being able to monitor individual ganglion cells will be the ultimate goal as a biomarker. For example, if you were testing a drug or even monitoring the progression of the disease so that you could very finely tune the treatment to each individual patient, so frequently and so quickly that you could prevent the loss of individual ganglion cells, you would ultimately be preserving vision.

Dr. Huberman: Retinal ganglion cells are the neurons that link the eye to the brain. The way they do that is by little wires that we call axons that actually exit the back of the eye in the area we call the optic nerve head.

They comprise the optic nerve and they’re literally like wires that plug the retina, the light-sensing neural tissue at the back of the eye to the brain, and then the brain makes sense of those neural signals so that it can understand, or you can understand, what an edge is or what a person's face is and who that person is. They're really remarkable cells in that sense.

Dr. Srinivasan: Retinal ganglion cells are the cells that are affected in glaucoma. Those are the cells that become sick and eventually die in glaucoma.

Dr. Goldberg: Right now all therapy for glaucoma is directed at lowering eye pressure, but the idea that we could develop therapies and test them in people that really target the retinal ganglion cells and the axon fibers going into the optic nerve — that, I think is the most exciting new frontier for the premise of restoring vision and protecting vision in glaucoma.

There are a couple of ways that we're looking at doing that. Neuroprotection is one. Neuroprotection refers to our ability to keep the cells alive despite the insult of glaucoma. Neuroenhancement is also very exciting. There's the idea that we could give the cells a ‘booster shot’ and take sick cells that weren't functioning for a patient's vision and make them more functional again and maybe make the patient see better in an acute or short time frame.

Without the Glaucoma Research Foundation seeding this collaborative effort, I don't see where the two neuroscientists and the two optical engineers would have come together to tackle this problem.

It's been enormously fun watching, over these last few years, the progress that we're making in the laboratory translate into progress that we're making on the engineering side and moving that right into human testing. I don't think any of that would have come to be without the seeding from the ‘Catalyst for a Cure’ program.

Dr. Huberman: About 10 or 15 years ago, there was very little understanding about the sequence of degenerative events leading to glaucoma. The first CFC [Catalyst for a Cure] group really beautifully defined what the sequence of events is.

Then when the second CFC group came in ¬— Jeff, Alf, Vivek and I ¬— we took it upon ourselves to try and take that information and apply it to understanding what are the best biomarkers, what are those going to be, what would they look like, and then to define and actually work with those biomarkers. And that's what we've done.

Dr. Goldberg: In the preceding years we made enormous progress identifying: what should we be trying to measure in glaucoma to provide new biomarkers for this disease. This past year has been very exciting because we've moved a number of these new biomarkers into human testing.

In a series of human clinical trials, we're now testing some of the new adaptive optics imaging modalities, some of the new OCT-based modalities. We're also testing a new kind of visual field test where we're actually measuring the signals that go from the eye to the brain in glaucoma patients.

Any or all of these, we think, will give us great new insight into the disease, into whether patients are progressing, and in particular into whether they're responding to new candidate therapies that we're beginning to test in our patients.

Dr. Huberman: We work as a team of four, but we communicate with the larger scientific community and the glaucoma community. I think that the opportunities to communicate with donors and patients and various arms of the research and clinical communities have really brought together a new avenue. It's like there's a new highway from the problem to the solution.

The field of glaucoma research, I think, has advanced tremendously, in no small part due to the support of the Glaucoma Research Foundation. I think that's absolutely clear.